We propose to continue and expand our ongoing prospective study on serum 25-hydroxyvitamin D (25(OH)D) levels and risk of multiple sclerosis (MS) among US military personnel. During the first phase of this project, we found that non-Hispanic white individuals with higher levels of serum 25(OH)D have a markedly reduced risk of developing MS. Results of dose-response analyses seemed to suggest a threshold effect -- at levels above 100 nmol/L MS risk was reduced by half as compared with levels below 100 nmol/L, whereas no significant changes in MS risk were observed at lower levels -- however, a moderate protective effect of lower levels of 25(OH)D could not be excluded because of the insufficient sample size. Further, risk of MS was ten times lower among individuals with 25(OH)D levels above 100 nmol/L before the age of 20 -- a result that supports the notion that adolescence could be a critical period for MS etiology. We now propose to expand this study by increasing our MS cases from 315 to 775 by extending our ongoing follow-up through 2011 in the US Army and Navy and including cases of MS occurring among Air Force personnel. This will allow us to explore more closely the potentially important associations with age and the nature of the dose-response relationship. We will also increase our sample size among blacks, increasing our power to examine these associations in this group. We also propose to expand our study to include examining the association between serum 25(OH)D and type 1 diabetes (T1D)-another autoimmune disease for which studies suggest a protective effect of vitamin D-among Army and Navy personnel. We expect to have 730 T1D cases for the analysis. The proposed investigation will continue to take advantage of the Department of Defense Serum Repository, which houses over 30 million serum samples from over 7 million US military personnel. Strengths of this study include not only the prospective design, but that multiple serum samples are available for most individuals, so that we can estimate long-term 25(OH)D status, as well as examine more closely potential age and seasonal effects of 25(OH)D on risk of MS or T1D. We propose to examine whether blood levels of vitamin D in healthy young adults predict their risk of developing multiple sclerosis and type 1 diabetes, which are disabling, chronic diseases primarily affecting individuals early in life, causing substantial personal and economic costs. This project, which takes advantage of a unique repository harboring over 30 million blood samples collected from healthy young adults, has the potential to identify interventions that could lead to the prevention of a significant number of cases of these diseases. [unreadable] [unreadable] [unreadable] [unreadable]